Evidence map›Paper›PMID 24586958›Full record

ArticlePloS one2014

Inhibition of TGFβ signaling increases direct conversion of fibroblasts to induced cardiomyocytes.

Jamie L Ifkovits, Russell C Addis, Jonathan A Epstein, John D Gearhart

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
110citing papers in PubMed, 1 pooled it
9.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

110 citing papers in PubMed, 1 synthesis or guideline pooled it, 173 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Next-generation direct reprogramming.Frontiers in cell and developmental biology · 2024
    Review
  10. Article
  11. Review
  12. Article
  13. Cellular reprogramming of fibroblasts in heart regeneration.Journal of molecular and cellular cardiology · 2023
    Review
  14. Review
  15. Review
  16. Genome Editing and Cardiac Regeneration.Advances in experimental medicine and biology · 2023
    Article
  17. Direct Cardiac Reprogramming: Current Status and Future Prospects.Advances in experimental medicine and biology · 2023
    Review
  18. Article
  19. Article
  20. Translational perspectives on cardiac reprogramming.Seminars in cell & developmental biology · 2022
    Review

50 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Jamie L IfkovitsDepartment of Cell and Developmental Biology, Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Russell C AddisDepartment of Cell and Developmental Biology, Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Jonathan A EpsteinDepartment of Cell and Developmental Biology, Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
John D GearhartDepartment of Cell and Developmental Biology, Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
University of Pennsylvania · US

Funding

Expansion of Cardiac and Hematopoietic Pregenitors by Wnt and NotchU01HL100395 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BERNSTEIN, IRWIN D, MOON, RANDALL TODD · 2009 to 2015
$8.4M
Expansion of cardiac and hematopoietic progenitors by Wnt and NotchU01HL100405 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI EPSTEIN, JONATHAN A., MORRISEY, EDWARD E · 2009 to 2015
$8.1M
NHLBI NIH HHS U01 HL100395NHLBI NIH HHS U01 HL100405
6 · The paper itself

Abstract

Recent studies have been successful at utilizing ectopic expression of transcription factors to generate induced cardiomyocytes (iCMs) from fibroblasts, albeit at a low frequency in vitro. This work investigates the influence of small molecules that have been previously reported to improve differentiation to cardiomyocytes as well as reprogramming to iPSCs in conjunction with ectopic expression of the transcription factors Hand2, Nkx2.5, Gata4, Mef2C, and Tbx5 on the conversion to functional iCMs. We utilized a reporter system in which the calcium indicator GCaMP is driven by the cardiac Troponin T promoter to quantify iCM yield. The TGFβ inhibitor, SB431542 (SB), was identified as a small molecule capable of increasing the conversion of both mouse embryonic fibroblasts and adult cardiac fibroblasts to iCMs up to ∼5 fold. Further characterization revealed that inhibition of TGFβ by SB early in the reprogramming process led to the greatest increase in conversion of fibroblasts to iCMs in a dose-responsive manner. Global transcriptional analysis at Day 3 post-induction of the transcription factors revealed an increased expression of genes associated with the development of cardiac muscle in the presence of SB compared to the vehicle control. Incorporation of SB in the reprogramming process increases the efficiency of iCM generation, one of the major goals necessary to enable the use of iCMs for discovery-based applications and for the clinic.

Indexed as

AnimalsBenzamidesCell DifferentiationDioxolesFibroblastsMiceMyocytes, CardiacReceptors, Transforming Growth Factor betaSignal TransductionTranscription FactorsTransforming Growth Factor beta4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideBenzamidesDioxolesReceptors, Transforming Growth Factor betaTranscription FactorsTransforming Growth Factor beta

Identifiers

PMID24586958
PMCPMC3935923
OpenAlexW2003756136

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.